Adolescent and young women are at high risk for HIV and STI acquisition. Developing novel, safe, preventative options for this population, such as vaginal microbicides, requires a thorough understanding of mucosal immunity in the female genital tract. Prior studies have evaluated the genital mucosal immune environment in adult women and indicate that protective factors in cervicovaginal fluid exhibit intrinsic activity against HIV, herpes simplex virus, and multiple types of pathogenic bacteria. However these data are lacking in young, adolescent women, and it remains unknown how innate immunity in the genital tract develops during adolescence. Moreover little is known of the functional components of genital mucosal immunity in young women infected with HIV, who may use microbicides with no knowledge of their infection or who may wish to use a microbicide to prevent infection with another STI or to prevent HIV transmission to their partner. This application addresses these knowledge gaps through the following specific aims: [(1) evaluate the differences in genital mucosal immunity in HIV uninfected females ages 13-21 years who are either within three years of menarche or greater than three years from menarche by comparing endogenous antimicrobial activity in genital secretions between the two groups and correlating this activity with specific immune mediators and vaginal microbiota populations;(2) evaluate the differences in genital mucosal immunity between a cohort of HIV infected young women ages 13-21 years and a cohort of healthy, uninfected women of similar age distribution by comparing endogenous antimicrobial activity in genital secretions and correlating this activity with specific immune mediators and vaginal microbiota populations.] The results of these studies will have significant implications for future studies of HIV and STI prevention and acquisition in young women. My objective is to become an independent investigator with expertise in STI acquisition and prevention in adolescent women. I have proposed a career development plan that incorporates mentorship in translational research methods, specialized training in novel laboratory techniques, individualized coursework, and participation in local and national meetings.
Prior studies of genital mucosal immunity in healthy, sexually mature women may not extrapolate to adolescent women or to young women already infected with HIV. The findings of these studies will therefore provide important baseline immunologic data for the evaluation of STI microbicide safety and efficacy in young women who are healthy or HIV infected. Moreover these studies will provide the foundation for larger, longitudial studies of HIV and STI acquisition in adolescent women.
|Pellett Madan, Rebecca; Masson, Lindi; Tugetman, Jessica et al. (2015) Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition. AIDS Res Hum Retroviruses 31:1153-9|
|Pellett Madan, Rebecca; Dezzutti, Charlene S; Rabe, Lorna et al. (2015) Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women. Am J Reprod Immunol 74:323-32|
|Mait-Kaufman, Jennifer; Fakioglu, Esra; Mesquita, Pedro M M et al. (2015) Chronic HIV Infection Is Associated with Upregulation of Proinflammatory Cytokine and Chemokine and Alpha Defensin Gene Expression in Colorectal Mucosa. AIDS Res Hum Retroviruses 31:615-22|
|Dara, Jasmeen S; Chen, Liang; Levi, Michael H et al. (2014) Microbiological and Genetic Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated From Pediatric Patients. J Pediatric Infect Dis Soc 3:e10-4|
|Pellett Madan, Rebecca; Herold, Betsy C (2013) HIV, sexual violence and special populations: adolescence and pregnancy. Am J Reprod Immunol 69 Suppl 1:61-7|
|Madan, Rebecca Pellett; Carpenter, Colleen; Fiedler, Tina et al. (2012) Altered biomarkers of mucosal immunity and reduced vaginal Lactobacillus concentrations in sexually active female adolescents. PLoS One 7:e40415|
|Keller, Marla J; Madan, Rebecca P; Shust, Gail et al. (2012) Changes in the soluble mucosal immune environment during genital herpes outbreaks. J Acquir Immune Defic Syndr 61:194-202|
|Kalyoussef, Sabah; Nieves, Edward; Dinerman, Ellen et al. (2012) Lactobacillus proteins are associated with the bactericidal activity against E. coli of female genital tract secretions. PLoS One 7:e49506|